Non-small-cell lung cancer (NSCLC) is amongst the most common tumors, which is responsible for most cancer-related mortality worldwide. Tumor-associated macrophages (TAMs) can regulate tumor microenvironment (TME) and malignant progression of NSCLC; however, the regulatory mechanisms of TAMs exosome (M2-Exo) in the context of NSCLC progression are still unclear. In this study, exosomes isolated from TAMs (M2-Exo) were subjected to FISH and RT-qPCR to explore hsa_circ_0000896 expressions in NSCLC specimens. Dual-luciferase reporter data were utilized to investigate hsa_circ_0000896 downstream targets. Transwell migration, 5-ethynyl-2′-deoxyuridine incorporation, cell counting, and wound hearing experiments were performed to assess NSCLC cell migration and proliferation. Hippocampus experiment was used to detect cellular metabolism. Mouse tumor xenograft model was constructed to assess the hsa_circ_0000896 roles in NSCLC metastasis and progressions. The data revealed that M2-Exo treatment promoted NSCLC cell proliferation and migrations. Hsa_circ_0000896 in M2-Exos mediated NSCLC malignant progression, which was ameliorated by downregulation of hsa_circ_0000896 expression. Both SLC2A3 and miR-503-5p were identified as hsa_circ_0000896 downstream targets. SLC2A3 overexpression or miR-503-5p suppression can reverse hsa_circ_0000896 silence inhibit effects to NSCLC malignant progression. The hippocampus experiment confirmed that downregulation of hsa_circ_0000896 inhibited aerobic glycolysis by regulating miR-503-5p/SLC2A3. A549-DDP were used to construct a subcutaneous tumor model, outcomes of which showed that downregulation of hsa_circ_0000896 increased NSCLC chemosensitivity. Together, our results revealed that exosomes from TAMs promoted glycolysis and malignant progression of NSCLC by delivering hsa_circ_0000896. And hsa_circ_0000896 can promote glycolysis by regulation miR-503-5p/SLC2A3.

circRNA is known to have regulatory functions across different cancers. Nevertheless, its regulatory functions in non-small cell lung cancer (NSCLC) are unknown. The present investigation aimed to research circ-FSCN1 expression in NSCLC cells and tissues employing high-throughput sequencing (HTS). NSCLC cells were investigated utilizing the CCK-8, EdU, and Transwell assays. Luciferase reporter assays were employed to verify circ-FSCN1 and its downstream target. Tumorigenesis and metastasis assays were performed to detect the role of circ-FSCN1 in NSCLC. Immunofluorescence was used to detect ROS deposition. The data indicated that the expression of hsa_circ_0004175 (circ-FSCN1) was elevated in NSCLC tissues and cells. The downregulation of circ-FSCN1 inhibited cellular migration and proliferation in the experiments. miR-506-3p downregulation or SLC7A1 overexpression reversed the suppression effects of sh-circ-FSCN1 on the proliferation and migration ability of H1299 and A549 cells. SLC7A1 overexpression reversed the inhibitory effects of miR-506-3p on the proliferation and migration ability of H1299 and A549 cells. The current investigation revealed that inhibiting miR-506-3p or overexpressing SLC7A1 reversed the enhancing effects of sh-circ-FSCN1 on ROS accumulation in H1299 and A549 cells. SLC7A1 overexpression reversed the enhancing effects of miR-506-3p on ROS accumulation in A549 and H1299 cells. Our investigation discovered that circ-FSCN1 affects ferroptosis and cell viability via the miR-506-3p/SLC7A1 pathway in NSCLC. circ-FSCN1 can function as a potential NSCLC diagnostic biomarker and therapy target.

Activation of antigen-presenting cells (APCs) via the stimulator of interferon genes (STING) signaling pathway is a promising strategy for cancer therapy. However, the rational engineering of a targeted synergistic immunomodulator and its morphological impact for STING activation remains elusive. Herein, we developed an APC-targeting lentinan-STING agonist immunomodulator with flexible and assembled morphological forms for cancer therapy. Lentinan (LN) exhibited intrinsic APC targeting and immune activation characteristics, and the conjugation between lentinan and a STING agonist (DMXAA) not only decreased the toxicity of lentinan toward APC cells, but also realized synergistic STING activation via lentinan and DMXAA. The flexible and assembled morphological forms were readily achieved by tuning the DMXAA loadings of the immunomodulators, denoted as LN-DMXAA(L) and LN-DMXAA(H). The flexible immunomodulator LN-DMXAA(L) with lower DMXAA loading potently induced macrophage reprogramming and dendritic cell maturation as compared with the assembled immunomodulator LN-DMXAA(H) and free drug DMXAA. In a 4 T1 tumor-bearing mice model, LN-DMXAA(L) significantly boosted tumor growth inhibition rate to 78.3% as compared with 46.2% for LN-DMXAA(H) and 27.8% for DMXAA by activating APCs and CD8+ T cells via the STING signaling pathway. Thus, this work highlights the conception of a flexible immune-activating polysaccharide-STING agonist immunomodulator for cancer therapy.

Background and purpose This study responds to the pressing need for novel therapeutic strategies to address key challenges in non-small cell lung cancer (NSCLC) treatment. It explores effective traditional Chinese medicine, investigates its molecular mechanism, and pursues the modernization of traditional Chinese medicine. The current research investigated how Solasonine (SS) extracted from Solanum nigrum L. may counter NSCLC by activating the ferroptosis pathway, while also elucidating the fundamental molecular mechanisms involved. Methods Proliferation (CCK8) and metastasis (wound healing) of A549/HCC1833 cells were assessed. Reactive oxygen species (ROS) production, proteomic sequencing, co-immunoprecipitation (Co-IP), and molecular docking mechanisms of the SS treatment group were analyzed. SLC7A11 regulation was evaluated using ferroptosis inhibitors and by ubiquitination assays. SS efficacy was tested in a subcutaneous/lung metastasis nude mouse model. Results SS suppressed NSCLC proliferation/metastasis by inducing ferroptosis. Proteomics revealed SS downregulated ferroptosis-related proteins and SLC7A11. SS promoted SLC7A11 ubiquitination/degradation via USP10/TRIM25 interactions, confirmed by Co-IP/docking. In vitro/vivo, SS increased ROS, inhibited tumor growth/metastasis, and activated ferroptosis pathways (reduced SLC7A11/GPX4/GSR/GSS). Immunohistochemistry confirmed the presence of ferroptosis markers in tumors. Conclusion SS triggers ferroptosis in NSCLC by disrupting USP10/TRIM25-mediated SLC7A11 stability. This study proposes a novel treatment strategy for NSCLC with a traditional Chinese medicine monomer.

Background: Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb Rabdosia rubescens with anticancer properties. Nevertheless, its effects on LC and the underlying mechanisms remain unknown. Methods: In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis in vivo. Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11. Result: Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration. Conclusion: In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.

Systemic sclerosis (SSc) is an autoimmune condition affecting several organs. It is identified by thickening of the dermis, connective tissue affected by collagen accumulation, and vascular injuries that induce hypoxia. The present study aimed to determine whether extracellular vesicles (EVs) from adipose-derived stem cells (ADSCs) attenuated bleomycin-induced skin fibrosis and oxidative stress in scleroderma. ADSCs and their EVs were separated and a bleomycin-induced SSc mouse model was constructed. High-throughput sequencing was employed to study abnormal expression of circular RNAs in SSc skin tissues with or without ADSC-EV treatment. The regulatory mechanism and targets were studied using bioinformatics analysis, luciferase reporting analysis, angiogenic differentiation experiments, and RT-qPCR detection analysis. EVs from ADSCs were successfully isolated. The exosome treatment prevented dermal thickening and fibrosis in bleomycin-induced scleroderma. In addition, circ-Zfyve9 was demonstrated to have an important function in ADSC-EV-mediated skin tissue protection. GPX4 and miR-135 were shown to be downstream targets of circ-Zfyve9. Overexpressing miR-135 or downregulating GPX4 reversed the promotion effects of circ-Zfyve9 on angiopoiesis by increasing lipidosome ROS in EPCs under hypoxic conditions. Overexpressing miR-135 or downregulating GPX4 reversed the inhibition effect of circ-Zfyve9 on fibrosis in myofibroblasts under hypoxic conditions. Overexpressing circ-Zfyve9 increased the therapeutic effect of ADSC-EVs. EVs from ADSCs attenuated bleomycin-induced skin fibrosis and oxidative stress in scleroderma via circ-Zfyve9 delivery.

IntroductionNasal inverted papilloma (NIP) is closely associated with human papillomavirus (HPV) infection, with HPV11 showing the highest expression levels in NIP tissues. However, the mechanism of its genomic integration remains incompletely understood. This study investigated frequent viral integration at the peroxisome proliferator-activated receptor alpha (PPARA) gene locus—a known regulator of autophagy—and its potential role in HPV11-mediated pathogenesis.MethodsHigh-throughput sequencing of HPV-positive specimens identified PPARA as a common integration site. HPV11 E6/E7 overexpression, PPARA overexpression, and PPARA knockdown models were established in human nasal epithelial cells (HNEpC). Cell proliferation, migration, and autophagy levels were assessed. The role of PPARA in proliferation and autophagy modulation was further validated using a nude mouse xenograft model. Additionally, the autophagy inhibitor 3-Methyladenine (3-MA) was applied to evaluate its effects on proliferation and migration.ResultsHPV11 E6/E7 overexpression significantly enhanced cell proliferation and migration. In contrast, PPARA overexpression promoted autophagy and suppressed proliferation and migration. Inhibition of autophagy by 3-MA reversed the suppressive effects mediated by PPARA. In vivo experiments confirmed the proliferative role of HPV11 E6/E7 and the autophagy-modulating function of PPARA.DiscussionHPV11 exerts dual effects on nasal mucosal cells: promoting proliferation and migration via E6/E7, while concurrently inducing an inhibitory effect through PPARA-mediated autophagy activation. The suppression of autophagy reversed the PPARA-driven inhibition, indicating a key role for the autophagy pathway. These findings suggest that PPARA targeting may be crucial in the pathogenesis of NIP, highlighting a complex interaction between HPV11 integration and host autophagy regulation.

Ultraviolet B (UVB) radiation contributes to solar dermatitis by inducing oxidative stress, inflammation, and skin barrier disruption. Portulaca oleracea polysaccharide (POP) possesses documented immunomodulatory properties, but its role in UVB-induced solar dermatitis remains unclear. In this study, we evaluated the photoprotective effects of POP using macrophage-based assays, keratinocyte co-culture systems, and a mouse model of UVB-induced solar dermatitis. POP skewed macrophages toward an M2-like phenotype and modulated their inflammatory responses. Furthermore, POP-conditioned macrophages attenuated oxidative stress in UVB-injured keratinocytes and enhanced their proliferation and migration. In vivo, topical application of POP ameliorated UVB-induced skin damage and barrier dysfunction; these protective effects were markedly attenuated following macrophage depletion. Collectively, our findings suggest that POP alleviates UVB-induced solar dermatitis, at least in part, through macrophage-mediated immunomodulation, supporting its further exploration as a natural candidate for photoprotective intervention.

BACKGROUND:Non-small cell lung cancer (NSCLC) remains a prevalent and malignant cancer globally, characterized by chemotherapy resistance. The aim of this study was focused on the potential of ginsenoside (Gn)-Rh2 from ginseng exosomes (Gn-Exos), a primary bioactive constituent of Panax ginseng, to enhance chemotherapy sensitivity in NSCLC. METHODS:In this study, Gn-Exo was isolated and identified. The intake and internal organ distribution of PKH26-labelled Gn-Exos was detected using immunofluorescence and in vivo imaging. Transwell migration, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, cell counting, and wound healing experiments were performed to assess NSCLC cell proliferation and migration. A mouse tumor xenograft model was constructed to assess the roles of Gn-Exos and the main active ingredient Gn-Rh2 in NSCLC progression and metastasis in vivo. RESULTS:Gn-Exos can inhibit the proliferation, migration, cancer growth, and pulmonary metastasis of NSCLC cells. Mass spectrometry analysis confirmed that the main component of Gn-Exos was Gn-Rh2. The results also showed that Gn-Rh2 inhibited the proliferation and migration of NSCLC cells in both in vivo and in vitro experiments. Comprehensive proteomic analysis identified ribonucleotide reductase regulatory subunit M2 (RRM2) and ubiquitin-specific protease 22 (USP22) as key targets significantly downregulated by Gn-Rh2. Experimental results demonstrated that Gn-Rh2 disrupts the interaction to USP22, disrupting the interaction between USP22 and RRM2, leading to ubiquitination degradation of RRM2. Animal experiments further confirmed that Gn-Rh2 sensitized NSCLC cells to chemotherapy, particularly cisplatin. CONCLUSION:These findings provide novel insights into the molecular mechanisms of Gn-Rh2 in enhancing chemotherapy sensitivity and suggest a promising therapeutic strategy for NSCLC.

Age-related osteoporosis is closely associated with osteoblast dysfunction, in which cellular senescence plays a key role. Trimethylamine N-oxide (TMAO), a gut microbiota–derived metabolite, is implicated in aging and metabolic diseases and has been linked to bone metabolism. However, whether TMAO impairs bone formation by regulating osteoblast senescence remains unclear. This study investigated the effects of TMAO on osteoblast senescence and osteogenic function, focusing on the cGAS–STING–NF-κB signaling axis. MC3T3-E1 cells were treated with TMAO to evaluate proliferation, cell cycle progression, senescence, and osteogenic differentiation. Cytosolic DNA release and activation of the cGAS–STING–NF-κB axis were assessed. In vivo, a chronic TMAO exposure model was established, combined with AAV9-mediated STING knockdown, and bone microarchitecture was analyzed by micro-CT. TMAO significantly inhibited proliferation and induced G0/G1 arrest in MC3T3-E1 cells without apparent cytotoxicity. It increased SA-β-gal–positive cells and upregulated senescence-associated markers, indicating a senescent phenotype. Functionally, TMAO suppressed osteogenic differentiation and mineralization and downregulated osteogenic proteins. Mechanistically, TMAO promoted abnormal release of mitochondrial DNA into the cytosol, activated the cGAS–STING pathway, and enhanced NF-κB signaling. STING overexpression exacerbated, whereas STING knockdown alleviated, TMAO-induced senescence and osteogenic impairment. NF-κB inhibition partially reversed these effects. In vivo, TMAO exposure impaired trabecular and cortical bone microarchitecture, which was partially improved by STING knockdown. TMAO induces osteoblast senescence and impairs osteogenic function, potentially via mtDNA-mediated activation of the cGAS–STING–NF-κB axis. These findings provide insight into age-related bone loss and suggest potential therapeutic targets.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with distinct geographic clustering, highly prevalent in southern China and Southeast Asia. Grape-derived exosome-like nanoparticles (GELNs) represent a promising natural delivery platform for cancer intervention; however, the intrinsic resveratrol (RSV) of GELNs and their regulatory effects on lipid metabolism in NPC remain poorly defined. In this study, GELNs were isolated from grape peels by ultracentrifugation and characterized morphologically and biochemically. The therapeutic efficacy of GELNs-RSV was evaluated in HNE-1 cells and nude mouse xenografts using CCK-8, Transwell, in vivo imaging and histological analyses. Transcriptomic profiling, pathway enrichment and gain-of-function experiments were applied to dissect molecular mechanisms. Results revealed that GELNs effectively delivered RSV into NPC cells, and markedly attenuated cell proliferation, migration and xenograft tumor growth. Mechanistically, GELNs-RSV repressed fatty acid synthase (FASN) expression and inactivated the MAPK pathway via decreased ERK phosphorylation, thereby disrupting lipid metabolism and constraining NPC progression. These findings identify GELNs as a natural RSV delivery system that targets the FASN/MAPK axis, providing preclinical evidence for the development of novel NPC therapeutic strategies.

Diabetic wound (DW) complications, driven by persistent oxidative stress, unresolved inflammation, and vascular dysfunction, present a critical clinical challenge. Although various polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. Plant-to-mammal regulation has provided an effective approach for chronic wound management in recent years, but the development of effective plant-based treatments remains challenging. The use of exosomes (Exos) from Chinese herbs is promising for wound healing. In the present study, Leonurus japonicus Houttuyn (YMC)-originating Exos were isolated and the YMC-Exo engineered hydrogel treatment inhibited stress microenvironment-induced endothelial cell and keratinocyte damage and accelerated DW healing (DWH). Mass spectrometry results for active constituent detection showed that YMC-Exos contained stachydrine (STA). In vitro and in vivo experiments confirmed that the STA treatment reversed stress microenvironment-induced endothelial cell and keratinocyte damage and promoted DWH by promoting Nrf2 expression. Limited proteolysis mass spectrometry detection revealed that KEAP1 was a downstream STA target. KEAP1 overexpression inhibited the nuclear translocation of Nrf2 after the STA treatment, suggesting that STA interacted with KEAP1 and promoted the nuclear translocation of Nrf2. Taken together, the results demonstrated that STA from YMC-Exo engineered hydrogel treatment improved hyperglycemia-induced stress microenvironment by directly binding and inhibiting KEAP1, thereby improving endothelial cell and keratinocyte function and accelerating DWH.

Impaired osteoblast differentiation is a central pathological event in osteoporosis. Forkhead box transcription factor D1 (FOXD1) is a key regulator of cellular metabolism, yet its precise role and upstream regulatory mechanisms during osteogenic differentiation remain poorly defined. We hypothesized that FOXD1 function might be modulated by the ubiquitin-proteasome system via the deubiquitinating enzyme USP13. Using an ovariectomy (OVX)-induced mouse osteoporosis model and MC3T3-E1 osteoprogenitor cells with Foxd1 or Usp13 knockdown/overexpression, we assessed osteogenic differentiation, glycolytic function, and the USP13-FOXD1 interaction. Results showed Foxd1 expression was upregulated during osteogenic induction. Overexpression of Foxd1 enhanced proliferation, differentiation, mineralization, and aerobic glycolysis, whereas knockdown suppressed these processes. Mechanistically, USP13 directly bound to FOXD1 and stabilized it by inhibiting proteasomal degradation via deubiquitination. Rescue experiments confirmed that FOXD1 is the critical downstream target of USP13, as Foxd1 overexpression reversed the impaired osteogenesis and suppressed glycolysis caused by Usp13 knockdown. In OVX mice, Usp13 overexpression improved bone microstructure and biomechanical strength in a FOXD1-dependent manner, while Foxd1 knockdown abolished these protective effects. This study is the first to elucidate that USP13 stabilizes FOXD1 through deubiquitination, driving aerobic glycolysis reprogramming, promoting osteogenic differentiation, and alleviating osteoporosis. This defines the "USP13-FOXD1-Glycolysis" axis as a pivotal regulatory mechanism, providing a potential therapeutic target for anti-osteoporosis strategies.

[This retracts the article DOI: 10.1016/j.omtn.2019.08.016.].

MEL suppresses the metastasis of NSCLC by targeting USP10 and promoting RNF20-mediated ubiquitination and degradation ofPSMA7.

BackgroundClinical studies have established an association between infections and circulating vitamin levels. However, the relationship stratified by specific pathogen types remains underexplored. More importantly, the causal direction of this association is still unclear.MethodsWe utilized summary-level data from genome-wide association studies (GWAS) of European ancestry, sourced from the UK Biobank (UKB) and FinnGen consortium. A two-sample, bidirectional Mendelian randomization (MR) analysis was employed to investigate the genetic causal relationships between infectious diseases (categorized as bacterial or viral) and circulating levels of vitamins A, B6, B12, C, D, 25-hydroxyvitamin D (25(OH)D), and E. The inverse variance weighted (IVW) method served as the primary analytical approach. Sensitivity analyses were conducted to validate the robustness of the findings. Furthermore, we employed the cecal ligation and puncture (CLP) model in mice to assess the impact of sepsis on serum 25(OH)D levels.ResultsGenetically predicted higher circulating vitamin E levels were associated with an increased risk of viral infection (OR = 1.45, 95% CI: 1.10–1.88). Conversely, genetic predisposition to bacterial infection was associated with lower circulating 25(OH)D levels (OR = 0.96, 95% CI: 0.93–0.99). In vivo experiments confirmed a significant decrease in serum 25(OH)D levels in CLP group mice compared to the Sham group (Sham: 90.7 ± 1.7 vs. CLP: 47.9 ± 5.6). No causal relationships were identified between infections and other vitamins.ConclusionThis study provides evidence for a potential causal link between elevated vitamin E levels and increased susceptibility to viral infection, as well as between bacterial infection and reduced 25(OH)D levels. Furthermore, our in vivo data demonstrated that sepsis (induced by intraperitoneal bacterial infection) led to a significant decrease in serum 25(OH)D levels.

Fluorescence imaging of subcellular structures is crucial for understanding cellular functions and disease mechanisms. However, existing fluorescent dyes are plagued by inadequate biocompatibility and insufficient stability, which impede the advancement of high-resolution, long-term, and live-cell imaging. In this work, we innovatively synthesized a novel nickel nanocluster encapsulated with ficin (Ficin-Ni NCs) through a straightforward biomineralization approach as a fluorescent probe for imaging the nucleus. The Ficin-Ni NCs with intense green fluorescence exhibited a particle size of approximately 1.56 nm, significant Stokes shift (110 nm), and remarkable stability (98 % fluorescence intensity after 14 days). Meanwhile, the Ni NCs demonstrated excellent biocompatibility, maintaining cell viability above 90 % for both Raw264.7 and HEK-293T cells at a concentration of 60 μg/mL. Significantly, DNA gel electrophoresis experiments, using ethidium bromide (EB) as a reference, confirmed the ability of the NCs to bind DNA. Furthermore, the as-prepared Ficin-Ni NCs could achieve precise imaging of cell nuclei consistent with 4',6-diamidino-2-phenylindole (DAPI) within 15 min in a variety of animal cells, including HEK-293T cells, Raw264.7, bullfrog erythrocytes, and human oral epithelial cells. Simultaneously, Ni NCs also demonstrated remarkable potential for visualizing the nuclear structures in plant cells, such as onion and cinnamon epidermal cells. Therefore, this innovative fluorescent probe, initially prepared via biomineralization, emerges as a promising alternative to traditional EB or DAPI dyes, paving the way for rapid response, effectiveness, and reusability in cellular imaging.

BACKGROUND:Lung cancer is a leading cause for cancer-related mortality across the globe. In the last decade, significant advancements have been made in the research of non-small cell lung cancer (NSCLC). However, new biotherapeutic drugs urgently need to be developed. This study investigated the regulating effect of hyperoside on NSCLC progression. METHODS:The colony formation assay and Cell Counting Kit-8 were used to detect cell proliferation. The Transwell assay was used to monitor cell migration. NSCLC growth in vivo was examined using a subcutaneous xenograft model. Proteomics, immunohistochemistry, and immunofluorescence analyses were used to detect anticancer regulatory mechanisms. RESULTS:The results showed that hyperoside treatment inhibited cell migration, proliferation, and tumor growth in NSCLC in vivo and in vitro. Also, hyperoside treatment promoted apoptosis and cell cycle S-phase arrest. Proteomics, immunohistochemistry, and immunofluorescence detection also showed that hyperoside treatment promoted autophagy-related protein 13 (ATG13)-mediated autophagy, which further increased NSCLC apoptosis. CONCLUSION:In summary, the findings illustrated that hyperoside treatment suppressed NSCLC progression by promotingATG13 expression and enhancing autophagy activation, finally promoting autophagy and apoptosis.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy driven by metabolic reprogramming, including dysregulated aerobic glycolysis and reactive oxygen species (ROS) signaling, which promote disease progression and therapeutic resistance. Although baicalein (BC) has demonstrated anti-tumor potential in various cancers, its specific role and molecular mechanisms in AML remain unclear. This study aimed to elucidate the effects and regulatory mechanisms of BC in AML. Network pharmacology analysis predicted BC's involvement in ROS regulation, myeloid differentiation, metabolic processes, and ferroptosis. In vitro experiments revealed that BC inhibited HL-60 cell proliferation and induced G0/G1 cell cycle arrest. Low concentrations of BC promoted ROS accumulation and myeloid differentiation, as evidenced by elevated CD11b and CD14 levels, which were reversed by ROS inhibitors. High concentrations of BC triggered ferroptosis via the SLC7A11/GSH/GPX4 pathway, confirmed by molecular docking and SLC7A11 overexpression. BC also suppressed aerobic glycolysis at both low and high concentrations. In vivo, BC significantly inhibited tumor progression in an HL-60 xenograft model by suppressing aerobic glycolysis. These findings demonstrate that BC modulates AML progression through concentration-dependent ROS accumulation, inducing differentiation at low doses and ferroptosis at high doses, offering a novel strategy for targeting the metabolism-oxidative stress axis in AML therapy.